This project concerns the isolation and biological and molecular characterization of C-type murine leukemia viruses (MuLVs). Present emphasis has been on analysis of the mechanism of action of the defective MuLV genome (BM5def) identified as the pathogenic element in LP-BM5 virus mixtures, which also contain replication competent, B-tropic ecotropic and MCF MuLVs. Infection of susceptible mice by LP-BM5 MuLV results in lymphoproliferation and progressive impairment of normal functions of the immune system involving both T- and B-cells, a syndrome termed murine AIDS (MAIDS). Pathogenesis involves interactions between T- and B- cells and with non-T, non-B lymphoid cells in which the role of expression of BM5def and helper virus has not been precisely defined. Restriction endonuclease mapping, molecular cloning and partial sequencing of BM5def and BM5eco, and immunoprecipitation analyses show that the 4.9Kb defective genome contains major deletions in the env and pol regions, as well as alterations in the pl2 region of gag resulting in an unusual 60-kDa precursor protein. By Southern blot analysis mouse cellular DNAs were found to exhibit strain-specific patterns of bands hybridizing with a probe for BM5def sequences. With appropriate restriction enzymes an extra-genomic 4.4Kb band has been detected in B-cell tumor lines and lymphoid tissues derived from infected mice, and studies are in progress to define the time of appearance and tissue specificity of viral integration and mRNA expression. In other, collaborative, studies it was found that subtle structural alterations in the highly conserved MuLV enhancers can alter disease phenotype; and the development of olfactory neuroblastoma in mice transgenic for adenovirus E1 genes was found to be associated with activation of endogenous MuLV.